Two theories address the origin of repeating patterns, such as hair follicles, limb digits, and intestinal villi, during development. The Turing reaction-diffusion system posits that interacting diffusible signals produced by static cells first define a prepattern that then induces cell rearrangements to produce an anatomical structure. The second theory, that of mesenchymal self-organisation, proposes that mobile cells can form periodic patterns of cell aggregates directly, without reference to any prepattern. Early hair follicle development is characterised by the rapid appearance of periodic arrangements of altered gene expression in the epidermis and prominent clustering of the adjacent dermal mesenchymal cells. We assess the contributions and interplay between reaction-diffusion and mesenchymal self-organisation processes in hair follicle patterning, identifying a network of fibroblast growth factor (FGF), wingless-related integration site (WNT), and bone morphogenetic protein (BMP) signalling interactions capable of spontaneously producing a periodic pattern. Using time-lapse imaging, we find that mesenchymal cell condensation at hair follicles is locally directed by an epidermal prepattern. However, imposing this prepattern's condition of high FGF and low BMP activity across the entire skin reveals a latent dermal capacity to undergo spatially patterned self-organisation in the absence of epithelial direction. This mesenchymal self-organisation relies on restricted transforming growth factor (TGF) β signalling, which serves to drive chemotactic mesenchymal patterning when reaction-diffusion patterning is suppressed, but, in normal conditions, facilitates cell movement to locally prepatterned sources of FGF. This work illustrates a hierarchy of periodic patterning modes operating in organogenesis.

• MeSH
• buněčná diferenciace MeSH
• inbrední kmeny myší MeSH
• kůže cytologie   embryologie   metabolismus   MeSH
• myši MeSH
• rozvržení tělního plánu MeSH
• signální transdukce MeSH
• stanovení celkové genové exprese MeSH
• transformující růstový faktor beta metabolismus   fyziologie   MeSH
• vlasový folikul embryologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

How the embryonic body axis is generated is a fundamental question in developmental biology. The molecular mechanisms involved in this process have been the subject of intensive studies using traditional model organisms during the last few decades, and the results have provided crucial information for understanding the formation of animal body plans. In particular, studies exploring the molecular nature of Spemann's organizer have revealed the intricate interactions underlying several signaling pathways (namely the Wnt/β-catenin, Nodal and Bmp pathways) that pattern the dorsoventral (DV) axis in vertebrate embryos. Furthermore, recent comparative studies have shown that many of these signaling interactions are also employed in other non-vertebrate model organisms for their early embryonic axis patterning. These results suggest that there is deep homology in DV patterning mechanisms among bilaterian animals and that these mechanisms may be traced back to the common ancestor of cnidarians and bilaterians. However, the mechanism by which the DV axis became inverted in the chordate lineage relative to the DV axis in other bilaterian animals remains unclear. Cephalochordata (i.e., amphioxus) represent a basal chordate group which occupies a key phylogenetic position for explorations of the origin of the chordate body plan. In this review, we summarize what is currently known regarding the developmental mechanisms that establish the DV axis in amphioxus embryos. By comparing this to what is known in vertebrates, we can start to hypothesize about the ancestral DV patterning mechanisms in chordates and discuss their possible evolutionary origins.

• MeSH
• cytoskelet metabolismus   MeSH
• embryo nesavčí embryologie   metabolismus   MeSH
• kopinatci embryologie   genetika   metabolismus   MeSH
• rozvržení tělního plánu genetika   MeSH
• signální transdukce genetika   MeSH
• vývojová regulace genové exprese * MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

When patterns are set during embryogenesis, it is expected that they are straightly established rather than subsequently modified. The patterning of the three mouse molars is, however, far from straight, likely as a result of mouse evolutionary history. The first-formed tooth signaling centers, called MS and R2, disappear before driving tooth formation and are thought to be vestiges of the premolars found in mouse ancestors. Moreover, the mature signaling center of the first molar (M1) is formed from the fusion of two signaling centers (R2 and early M1). Here, we report that broad activation of Edar expression precedes its spatial restriction to tooth signaling centers. This reveals a hidden two-step patterning process for tooth signaling centers, which was modeled with a single activator-inhibitor pair subject to reaction-diffusion (RD). The study of Edar expression also unveiled successive phases of signaling center formation, erasing, recovering, and fusion. Our model, in which R2 signaling center is not intrinsically defective but erased by the broad activation preceding M1 signaling center formation, predicted the surprising rescue of R2 in Edar mutant mice, where activation is reduced. The importance of this R2-M1 interaction was confirmed by ex vivo cultures showing that R2 is capable of forming a tooth. Finally, by introducing chemotaxis as a secondary process to RD, we recapitulated in silico different conditions in which R2 and M1 centers fuse or not. In conclusion, pattern formation in the mouse molar field relies on basic mechanisms whose dynamics produce embryonic patterns that are plastic objects rather than fixed end points.

• MeSH
• biologické modely * MeSH
• chemotaxe MeSH
• epitel embryologie   metabolismus   MeSH
• mutantní kmeny myší MeSH
• myši MeSH
• receptor Edar genetika   metabolismus   MeSH
• rozvržení tělního plánu * MeSH
• signální transdukce * MeSH
• vlasy, chlupy embryologie   MeSH
• vývojová regulace genové exprese MeSH
• zubní zárodek embryologie   metabolismus   MeSH
• zuby embryologie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The patterning of repeated structures is a major theme in developmental biology, and the inter-relationship between spacing and size of such structures is an unresolved issue. Fungiform papillae are repeated epithelial structures that house taste buds on the anterior tongue. Here, we report that FGF signaling is a crucial regulator of fungiform papillae development. We found that mesenchymal FGF10 controls the size of the papillary area, while overall patterning remains unchanged. Our results show that FGF signaling negatively affects the extent of canonical Wnt signaling, which is the main activation pathway during fungiform papillae development; however, this effect does not occur at the level of gene transcription. Rather, our experimental data, together with computational modeling, indicate that FGF10 modulates the range of Wnt effects, likely via induction of Sostdc1 expression. We suggest that modification of the reach of Wnt signaling could be due to local changes in morphogen diffusion, representing a novel mechanism in this tissue context, and we propose that this phenomenon might be involved in a broader array of mammalian developmental processes.

• MeSH
• biologické modely MeSH
• chuťové pohárky embryologie   metabolismus   MeSH
• fibroblastový růstový faktor 10 nedostatek   genetika   metabolismus   MeSH
• intracelulární signální peptidy a proteiny nedostatek   genetika   metabolismus   MeSH
• kostní morfogenetické proteiny genetika   metabolismus   MeSH
• membránové proteiny nedostatek   genetika   metabolismus   MeSH
• myši knockoutované MeSH
• myši transgenní MeSH
• myši MeSH
• počítačová simulace MeSH
• proteiny hedgehog genetika   metabolismus   MeSH
• rozvržení tělního plánu genetika   fyziologie   MeSH
• signální dráha Wnt * MeSH
• těhotenství MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Formation of a dorsoventral axis is a key event in the early development of most animal embryos. It is well established that bone morphogenetic proteins (Bmps) and Wnts are key mediators of dorsoventral patterning in vertebrates. In the cephalochordate amphioxus, genes encoding Bmps and transcription factors downstream of Bmp signaling such as Vent are expressed in patterns reminiscent of those of their vertebrate orthologues. However, the key question is whether the conservation of expression patterns of network constituents implies conservation of functional network interactions, and if so, how an increased functional complexity can evolve. Using heterologous systems, namely by reporter gene assays in mammalian cell lines and by transgenesis in medaka fish, we have compared the gene regulatory network implicated in dorsoventral patterning of the basal chordate amphioxus and vertebrates. We found that Bmp but not canonical Wnt signaling regulates promoters of genes encoding homeodomain proteins AmphiVent1 and AmphiVent2. Furthermore, AmphiVent1 and AmphiVent2 promoters appear to be correctly regulated in the context of a vertebrate embryo. Finally, we show that AmphiVent1 is able to directly repress promoters of AmphiGoosecoid and AmphiChordin genes. Repression of genes encoding dorsal-specific signaling molecule Chordin and transcription factor Goosecoid by Xenopus and zebrafish Vent genes represents a key regulatory interaction during vertebrate axis formation. Our data indicate high evolutionary conservation of a core Bmp-triggered gene regulatory network for dorsoventral patterning in chordates and suggest that co-option of the canonical Wnt signaling pathway for dorsoventral patterning in vertebrates represents one of the innovations through which an increased morphological complexity of vertebrate embryo is achieved.

• MeSH
• 5' nepřekládaná oblast MeSH
• Chordata genetika   MeSH
• dánio pruhované embryologie   genetika   MeSH
• embryo nesavčí MeSH
• fylogeneze MeSH
• genetická variace genetika   fyziologie   MeSH
• genové regulační sítě MeSH
• homeodoménové proteiny genetika   MeSH
• konzervovaná sekvence genetika   MeSH
• kultivované buňky MeSH
• lidé MeSH
• molekulární evoluce MeSH
• molekulární sekvence - údaje MeSH
• Oryzias embryologie   genetika   MeSH
• protein goosecoid genetika   MeSH
• rozvržení tělního plánu genetika   MeSH
• sekvence aminokyselin MeSH
• sekvence nukleotidů MeSH
• sekvenční homologie aminokyselin MeSH
• vývojová regulace genové exprese MeSH
• Xenopus laevis embryologie   genetika   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Occurrence of stomata on both leaf surfaces (amphistomaty) promotes higher stomatal conductance and photosynthesis while simultaneously increasing exposure to potential disease agents in black cottonwood (Populus trichocarpa). A genome-wide association study (GWAS) with 2.2M single nucleotide polymorphisms generated through whole-genome sequencing found 280 loci associated with variation in adaxial stomatal traits, implicating genes regulating stomatal development and behavior. Strikingly, numerous loci regulating plant growth and response to biotic and abiotic stresses were also identified. The most significant locus was a poplar homologue of SPEECHLESS (PtSPCH1). Individuals possessing PtSPCH1 alleles associated with greater adaxial stomatal density originated primarily from environments with shorter growing seasons (e.g. northern latitudes, high elevations) or with less precipitation. PtSPCH1 was expressed in developing leaves but not developing stem xylem. In developing leaves, RNA sequencing showed patterns of coordinated expression between PtSPCH1 and other GWAS-identified genes. The breadth of our GWAS results suggests that the evolution of amphistomaty is part of a larger, complex response in plants. Suites of genes underpin this response, retrieved through genetic association to adaxial stomata, and show coordinated expression during development. We propose that the occurrence of amphistomaty in P. trichocarpa involves PtSPCH1 and reflects selection for supporting rapid growth over investment in immunity.

• MeSH
• alely MeSH
• celogenomová asociační studie MeSH
• druhová specificita MeSH
• fenotyp MeSH
• genotyp MeSH
• imunita rostlin genetika   MeSH
• jednonukleotidový polymorfismus genetika   MeSH
• kvantitativní znak dědičný MeSH
• podnebí MeSH
• Populus genetika   růst a vývoj   imunologie   fyziologie   MeSH
• průduchy rostlin genetika   fyziologie   MeSH
• regulace genové exprese u rostlin MeSH
• rostlinné geny MeSH
• rostlinné proteiny genetika   metabolismus   MeSH
• rozvržení tělního plánu * MeSH
• vývoj rostlin MeSH
• zeměpis MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The Arabidopsis (Arabidopsis thaliana) gynoecium consists of two congenitally fused carpels made up of two lateral valve domains and two medial domains, which retain meristematic properties and later fuse to produce the female reproductive structures vital for fertilization. Polar auxin transport (PAT) is important for setting up distinct apical auxin signaling domains in the early floral meristem remnants allowing for lateral domain identity and outgrowth. Crosstalk between auxin and cytokinin plays an important role in the development of other meristematic tissues, but hormone interaction studies to date have focused on more accessible later-stage gynoecia and the spatiotemporal interactions pivotal for patterning of early gynoecium primordia remain unknown. Focusing on the earliest stages, we propose a cytokinin-auxin feedback model during early gynoecium patterning and hormone homeostasis. Our results suggest that cytokinin positively regulates auxin signaling in the incipient gynoecial primordium and strengthen the concept that cytokinin regulates auxin homeostasis during gynoecium development. Specifically, medial cytokinin promotes auxin biosynthesis components [YUCCA1/4 (YUC1/4)] in, and PINFORMED7 (PIN7)-mediated auxin efflux from, the medial domain. The resulting laterally focused auxin signaling triggers ARABIDOPSIS HISTIDINE PHOSPHOTRANSFER PROTEIN6 (AHP6), which then represses cytokinin signaling in a PAT-dependent feedback. Cytokinin also down-regulates PIN3, promoting auxin accumulation in the apex. The yuc1, yuc4, and ahp6 mutants are hypersensitive to exogenous cytokinin and 1-napthylphthalamic acid (NPA), highlighting their role in mediolateral gynoecium patterning. In summary, these mechanisms self-regulate cytokinin and auxin signaling domains, ensuring correct domain specification and gynoecium development.

• MeSH
• Arabidopsis embryologie   genetika   metabolismus   MeSH
• biologické modely MeSH
• biologický transport MeSH
• cytokininy metabolismus   MeSH
• homeostáza MeSH
• květy embryologie   MeSH
• kyseliny indoloctové metabolismus   MeSH
• proteiny huseníčku genetika   metabolismus   MeSH
• regulace genové exprese u rostlin MeSH
• regulátory růstu rostlin metabolismus   MeSH
• rostlinné geny MeSH
• rozvržení tělního plánu * MeSH
• signální transdukce * MeSH
• upregulace MeSH
• Publikační typ
• časopisecké články MeSH

Rodents are characterized by continuously renewing incisors whose growth is fueled by epithelial and mesenchymal stem cells housed in the proximal compartments of the tooth. The epithelial stem cells reside in structures known as the labial (toward the lip) and lingual (toward the tongue) cervical loops (laCL and liCL, respectively). An important feature of the rodent incisor is that enamel, the outer, highly mineralized layer, is asymmetrically distributed, because it is normally generated by the laCL but not the liCL. Here, we show that epithelial-specific deletion of the transcription factor Islet1 (Isl1) is sufficient to drive formation of ectopic enamel by the liCL stem cells, and also that it leads to production of altered enamel on the labial surface. Molecular analyses of developing and adult incisors revealed that epithelial deletion of Isl1 affected multiple, major pathways: Bmp (bone morphogenetic protein), Hh (hedgehog), Fgf (fibroblast growth factor), and Notch signaling were upregulated and associated with liCL-generated ectopic enamel; on the labial side, upregulation of Bmp and Fgf signaling, and downregulation of Shh were associated with premature enamel formation. Transcriptome profiling studies identified a suite of differentially regulated genes in developing Isl1 mutant incisors. Our studies demonstrate that ISL1 plays a central role in proper patterning of stem cell-derived enamel in the incisor and indicate that this factor is an important upstream regulator of signaling pathways during tooth development and renewal. © 2017 American Society for Bone and Mineral Research.

• MeSH
• delece genu MeSH
• epitel embryologie   metabolismus   MeSH
• fyziologická kalcifikace * MeSH
• mandibula metabolismus   MeSH
• mutace genetika   MeSH
• myši MeSH
• orgánová specificita MeSH
• proteiny s homeodoménou LIM genetika   metabolismus   MeSH
• řezáky embryologie   metabolismus   MeSH
• rozvržení tělního plánu * MeSH
• sekvenční analýza RNA MeSH
• signální transdukce MeSH
• stanovení celkové genové exprese MeSH
• transkripční faktory genetika   metabolismus   MeSH
• vývojová regulace genové exprese MeSH
• zubní sklovina embryologie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVE: To investigate the distribution of patient-reported outcomes (PROs) in patients with axial spondyloarthritis (axSpA) initiating a tumor necrosis factor inhibitor (TNFi), to assess the proportion reaching PRO "remission" across registries and treatment series, and to compare patients registered to fulfill the modified New York (mNY) criteria for ankylosing spondylitis (AS) vs patients with nonradiographic axSpA (nr-axSpA). METHODS: Fifteen European registries contributed PRO scores for pain, fatigue, patient global assessment (PtGA), Bath Ankylosing Spondylitis (AS) Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI), and Health Assessment Questionnaire (HAQ) from 19,498 patients with axSpA. Changes in PROs and PRO remission rates (definitions: ≤ 20 mm for pain, fatigue, PtGA, BASDAI, and BASFI; ≤ 0.5 for HAQ) were calculated at 6, 12, and 24 months of treatment. RESULTS: Heterogeneity in baseline characteristics and outcomes between registries were observed. In pooled data, 6 months after the start of a first TNFi, pain score was reduced by approximately 60% (median at baseline/6/12/24 months: 65/25/20/20 mm) in patients on treatment. Similar patterns were observed for fatigue (68/32/30/25 mm), PtGA (66/29/21/20 mm), BASDAI (58/26/21/19 mm), BASFI (46/20/16/16 mm), and HAQ (0.8/0.4/0.2/0.2). Patients with AS (n = 3281) had a slightly better response than patients with nr-axSpA (n = 993). The Lund Efficacy Index (LUNDEX)-adjusted remission rates at 6 months for pain/fatigue/PtGA/BASDAI/BASFI/HAQ were 39%/30%/38%/34%/35%/48% for the AS cohort and 30%/21%/26%/24%/33%/47% for the nr-axSpA cohort. Better PRO responses were seen with a first TNFi compared to a second and third TNFi. CONCLUSION: Patients with axSpA starting a TNFi achieved high PRO remission rates, most pronounced in those fulfilling the mNY criteria and for the first TNFi.

• MeSH
• ankylózující spondylitida * farmakoterapie   MeSH
• bolest MeSH
• inhibitory TNF terapeutické užití   MeSH
• lidé MeSH
• non-radiografická axiální spondyloartritida * MeSH
• spondylartritida * farmakoterapie   MeSH
• TNF-alfa MeSH
• únava farmakoterapie   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

In many arthropods, there is a change in relative segment size during post-embryonic development, but how segment differential growth is produced is little known. A new dataset of the highest quality specimens of the 429 Myr old trilobite Aulacopleura koninckii provides an unparalleled opportunity to investigate segment growth dynamics and its control in an early arthropod. Morphometric analysis across nine post-embryonic stages revealed a growth gradient in the trunk of A. koninckii. We contrastively tested different growth models referable to two distinct hypotheses of growth control for the developing trunk: (i) a segment-specific control, with individual segments having differential autonomous growth progression, and (ii) a regional control, with segment growth depending on their relative position along the main axis. We show that the trunk growth pattern of A. koninckii was consistent with a regional growth control producing a continuous growth gradient that was stable across all developmental stages investigated. The specific posterior-to-anterior decaying shape of the growth gradient suggests it deriving from the linear transduction of a graded signal, similar to those commonly provided by morphogens. A growth control depending on a form of positional specification, possibly realized through the linear interpretation of a graded signal, may represent the primitive condition for arthropod differential growth along the main body axis, from which the diverse and generally more complex forms of growth control in subsequent arthropods have evolved.

• MeSH
• biologické modely * MeSH
• členovci anatomie a histologie   růst a vývoj   MeSH
• regresní analýza MeSH
• rozvržení tělního plánu fyziologie   MeSH
• tělesné váhy a míry MeSH
• zkameněliny * MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• srovnávací studie MeSH
• Geografické názvy
• Česká republika MeSH